Anti-cancer activity of nitrones in the Apc(Min/+) model of colorectal cancer

Free Radic Res. 2010 Jan;44(1):108-17. doi: 10.3109/10715760903321796.

Abstract

Abstract The nitrones of alpha-phenyl-tert-butyl nitrone (PBN) and 4-hydroxyl-PBN (4-OH-PBN) that have anti-cancer activity in models of liver cancer and glioblastomas were tested in the ApcMin/+ mouse model. Mice were administered PBN and 4-OH-PBN in drinking water and intestinal tumour size and number assessed after 3-4 months. Throughout the experiment, contrast-enhanced magnetic resonance imaging (MRI) was used to monitor colon tumours. MRI data showed a time-dependent significant increase in total colonic signal intensity in sham-treated mice, but a significant decrease for PBN-treated mice and slight decrease for 4-OHPBN treated mice, probably due to the limited water solubility of 4-OH-PBN. Final pathological and percentage survival data agreed with the MRI data. PBN had little effect on oxaliplatin-mediated killing of HCT116 colon cancer cells and caused only a slight decrease in the amount of active fraction caspase 3 in oxaliplatin-treated cells. PBN has significant anti-cancer activity in this model of intestinal neoplasia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / drug therapy
  • Adenoma / genetics
  • Adenoma / mortality
  • Adenoma / pathology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Genes, APC*
  • HCT116 Cells
  • Humans
  • Loss of Heterozygosity / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nitrogen Oxides / pharmacology*
  • Nitrogen Oxides / therapeutic use
  • Survival Analysis

Substances

  • Antineoplastic Agents
  • Nitrogen Oxides
  • nitrones